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• W2116714531 abstract "Background Persistent reporter gene and cystic fibrosis transmembrane conductance regulator (CFTR) nasal airway gene expression can be achieved with a single lentiviral (LV) gene vector dosing when coupled with a preparatory lysophosphatidylcholine (LPC) airway pre-treatment. In the present study, we characterised the duration of gene expression in individual cystic fibrosis (CF) knockout mice (cftrtm1unc) over their lifetimes. Methods CF mouse nasal airways were treated with LV-Rx, a mixture of a therapeutic LV-CFTR gene vector and a LV-luciferase reporter gene vector, after pre-treatment with LPC. Control groups received either PBS sham pre-treatment followed by LV-Rx, or LPC prior to delivery of a LV vector containing no transgene (LV-MT). Airway reporter gene expression was monitored by bioluminescence, and functional CFTR expression was assessed via nasal transepithelial potential difference measurements at regular intervals up to 21 months. The presence of the CFTR transgene in the nasal septa, liver and spleen tissues were assessed by a quantitative polymerase chain reaction. Circulating antibodies to the vector glycoprotein envelope and to the luciferase protein were also measured. Results The combined use of LPC and LV gene vectors in the nasal airway produced enhanced and sustained luciferase and CFTR gene expression lasting at least 12 months. Improved survival was also observed in CF knockout mice treated with the LV vector mixture compared to all control CF mouse groups. Conclusions The present study showed that our airway pre-treatment and gene delivery technique resulted in sustained functional CFTR expression and improved survival in CF mice. Copyright © 2014 John Wiley & Sons, Ltd." @default.
• W2116714531 created "2016-06-24" @default.
• W2116714531 creator A5011387086 @default.
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• W2116714531 date "2014-09-01" @default.
• W2116714531 modified "2023-09-27" @default.
• W2116714531 title "Long-term therapeutic and reporter gene expression in lentiviral vector treated cystic fibrosis mice" @default.
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• W2116714531 doi "https://doi.org/10.1002/jgm.2778" @default.
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